ES2250177T3 - Compuestos heteropoliciclicos y su uso como antagonistas de receptores de glutamato metabotropico. - Google Patents
Compuestos heteropoliciclicos y su uso como antagonistas de receptores de glutamato metabotropico.Info
- Publication number
- ES2250177T3 ES2250177T3 ES00955657T ES00955657T ES2250177T3 ES 2250177 T3 ES2250177 T3 ES 2250177T3 ES 00955657 T ES00955657 T ES 00955657T ES 00955657 T ES00955657 T ES 00955657T ES 2250177 T3 ES2250177 T3 ES 2250177T3
- Authority
- ES
- Spain
- Prior art keywords
- pyridyl
- oxazole
- oxadiazole
- cyanophenyl
- chloro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 57
- 102000016193 Metabotropic glutamate receptors Human genes 0.000 title description 47
- 108010010914 Metabotropic glutamate receptors Proteins 0.000 title description 47
- 239000005557 antagonist Substances 0.000 title description 14
- -1 3- (2-pyridyl) -5-phenyl-1, 3, 4-oxadiazole Chemical compound 0.000 claims abstract description 45
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract description 23
- CQXOVXIKDZNZMV-UHFFFAOYSA-N 2-(3-chlorophenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound ClC1=CC=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 CQXOVXIKDZNZMV-UHFFFAOYSA-N 0.000 claims abstract description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 10
- 150000003839 salts Chemical class 0.000 claims abstract description 10
- XKZXZXODZDSMKN-UHFFFAOYSA-N 3-[3-(5-methoxypyridin-2-yl)-1,2,4-oxadiazol-5-yl]benzonitrile Chemical compound N1=CC(OC)=CC=C1C1=NOC(C=2C=C(C=CC=2)C#N)=N1 XKZXZXODZDSMKN-UHFFFAOYSA-N 0.000 claims abstract description 9
- NFNZGNPPPSUBSN-UHFFFAOYSA-N 5-(3,5-dimethoxyphenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound COC1=CC(OC)=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 NFNZGNPPPSUBSN-UHFFFAOYSA-N 0.000 claims abstract description 9
- DKASLOPISBVXCX-UHFFFAOYSA-N 3-pyridin-2-yl-5-[3-(trifluoromethoxy)phenyl]-1,2,4-oxadiazole Chemical compound FC(F)(F)OC1=CC=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 DKASLOPISBVXCX-UHFFFAOYSA-N 0.000 claims abstract description 8
- NGKWCJCCZGCLID-UHFFFAOYSA-N 5-(2-chlorophenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound ClC1=CC=CC=C1C1=NC(C=2N=CC=CC=2)=NO1 NGKWCJCCZGCLID-UHFFFAOYSA-N 0.000 claims abstract description 8
- PBVARAUVAZZUHN-UHFFFAOYSA-N 5-(3,5-dimethoxyphenyl)-3-(5-fluoropyridin-2-yl)-1,2,4-oxadiazole Chemical compound COC1=CC(OC)=CC(C=2ON=C(N=2)C=2N=CC(F)=CC=2)=C1 PBVARAUVAZZUHN-UHFFFAOYSA-N 0.000 claims abstract description 7
- GIHMKZCHBTWVSO-UHFFFAOYSA-N 5-(2,3-difluorophenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound FC1=CC=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1F GIHMKZCHBTWVSO-UHFFFAOYSA-N 0.000 claims abstract description 6
- YYKRPCBJFTUNFZ-UHFFFAOYSA-N 5-(3-nitrophenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound [O-][N+](=O)C1=CC=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 YYKRPCBJFTUNFZ-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 6
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims abstract description 5
- 125000002877 alkyl aryl group Chemical group 0.000 claims abstract description 5
- 125000003118 aryl group Chemical group 0.000 claims abstract description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 5
- 239000000203 mixture Substances 0.000 claims description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 16
- 229930195712 glutamate Natural products 0.000 claims description 16
- 201000010099 disease Diseases 0.000 claims description 12
- HFGWLRAJYOVQAY-UHFFFAOYSA-N 2-(3-bromophenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound BrC1=CC=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 HFGWLRAJYOVQAY-UHFFFAOYSA-N 0.000 claims description 8
- FPYLVHWPDOYNOI-UHFFFAOYSA-N 4-pyridin-2-yl-2-(2,3,6-trifluorophenyl)-1,3-oxazole Chemical compound FC1=CC=C(F)C(C=2OC=C(N=2)C=2N=CC=CC=2)=C1F FPYLVHWPDOYNOI-UHFFFAOYSA-N 0.000 claims description 8
- 208000012902 Nervous system disease Diseases 0.000 claims description 8
- 208000035475 disorder Diseases 0.000 claims description 8
- XZDUVAVPEQYRJT-UHFFFAOYSA-N 3-(4-pyridin-2-yl-1,3-oxazol-2-yl)benzonitrile Chemical compound N#CC1=CC=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 XZDUVAVPEQYRJT-UHFFFAOYSA-N 0.000 claims description 7
- 208000024827 Alzheimer disease Diseases 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- NEBUBOGLNXERLF-UHFFFAOYSA-N 3-chloro-5-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)benzonitrile Chemical compound ClC1=CC(C#N)=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 NEBUBOGLNXERLF-UHFFFAOYSA-N 0.000 claims description 6
- OTAZWJWYCGCZPY-UHFFFAOYSA-N 3-pyridin-2-yl-5-(2,3,6-trifluorophenyl)-1,2,4-oxadiazole Chemical compound FC1=CC=C(F)C(C=2ON=C(N=2)C=2N=CC=CC=2)=C1F OTAZWJWYCGCZPY-UHFFFAOYSA-N 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- YXDVCVJVOFDWQF-UHFFFAOYSA-N 2-(2-chlorophenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound ClC1=CC=CC=C1C1=NC(C=2N=CC=CC=2)=CO1 YXDVCVJVOFDWQF-UHFFFAOYSA-N 0.000 claims description 5
- BRSJLLPXGUAIGO-UHFFFAOYSA-N 3-[3-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-1,2,4-oxadiazol-5-yl]benzonitrile Chemical compound ClC1=CC(C(F)(F)F)=CN=C1C1=NOC(C=2C=C(C=CC=2)C#N)=N1 BRSJLLPXGUAIGO-UHFFFAOYSA-N 0.000 claims description 5
- GELAFISMURFRCA-UHFFFAOYSA-N 3-fluoro-5-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)benzonitrile Chemical compound FC1=CC(C#N)=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 GELAFISMURFRCA-UHFFFAOYSA-N 0.000 claims description 5
- PREUPKHXEHMSKI-UHFFFAOYSA-N 5-(5-chloro-2-methoxyphenyl)-3-pyridin-2-yl-1,2,4-oxadiazole Chemical compound COC1=CC=C(Cl)C=C1C1=NC(C=2N=CC=CC=2)=NO1 PREUPKHXEHMSKI-UHFFFAOYSA-N 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- AAWCNLJAPJLNKK-UHFFFAOYSA-N 2-(2,3-dichlorophenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound ClC1=CC=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1Cl AAWCNLJAPJLNKK-UHFFFAOYSA-N 0.000 claims description 4
- RJOREFFZIBPFKY-UHFFFAOYSA-N 2-(2,3-difluorophenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound FC1=CC=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1F RJOREFFZIBPFKY-UHFFFAOYSA-N 0.000 claims description 4
- LRFMDDYKWJYVBK-UHFFFAOYSA-N 2-(2,5-difluorophenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound FC1=CC=C(F)C(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 LRFMDDYKWJYVBK-UHFFFAOYSA-N 0.000 claims description 4
- DEMSILUPLXBKQE-UHFFFAOYSA-N 2-(2-chloro-5-methylsulfanylphenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound CSC1=CC=C(Cl)C(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 DEMSILUPLXBKQE-UHFFFAOYSA-N 0.000 claims description 4
- ASQZRZJOTGTSSV-UHFFFAOYSA-N 2-(3,5-dichlorophenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound ClC1=CC(Cl)=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 ASQZRZJOTGTSSV-UHFFFAOYSA-N 0.000 claims description 4
- YHRDDEHPQTZUOC-UHFFFAOYSA-N 2-(3,5-difluorophenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound FC1=CC(F)=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 YHRDDEHPQTZUOC-UHFFFAOYSA-N 0.000 claims description 4
- LPMYOKHUPLYHGH-UHFFFAOYSA-N 2-(3,5-dimethoxyphenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound COC1=CC(OC)=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 LPMYOKHUPLYHGH-UHFFFAOYSA-N 0.000 claims description 4
- DVWPIPCIVDZTFL-UHFFFAOYSA-N 2-(3-chloro-5-fluorophenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound FC1=CC(Cl)=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 DVWPIPCIVDZTFL-UHFFFAOYSA-N 0.000 claims description 4
- SIWHIGOKGZLPDD-UHFFFAOYSA-N 2-(3-methoxyphenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound COC1=CC=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 SIWHIGOKGZLPDD-UHFFFAOYSA-N 0.000 claims description 4
- MMOZNJWTGXWZAK-UHFFFAOYSA-N 2-(3-methylphenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound CC1=CC=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 MMOZNJWTGXWZAK-UHFFFAOYSA-N 0.000 claims description 4
- VVAAKNGCCMGISN-UHFFFAOYSA-N 2-(3-nitrophenyl)-4-pyridin-2-yl-1,3-oxazole Chemical compound [O-][N+](=O)C1=CC=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 VVAAKNGCCMGISN-UHFFFAOYSA-N 0.000 claims description 4
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- KZOBYFBUONCLFZ-UHFFFAOYSA-N 3-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)benzonitrile Chemical compound N#CC1=CC=CC(C=2ON=C(N=2)C=2N=CC=CC=2)=C1 KZOBYFBUONCLFZ-UHFFFAOYSA-N 0.000 claims description 4
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- PURMTHHDJDASBS-UHFFFAOYSA-N 3-fluoro-5-(4-pyridin-2-yl-1,3-oxazol-2-yl)benzonitrile Chemical compound FC1=CC(C#N)=CC(C=2OC=C(N=2)C=2N=CC=CC=2)=C1 PURMTHHDJDASBS-UHFFFAOYSA-N 0.000 claims description 4
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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Landscapes
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- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
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| US14946499P | 1999-08-19 | 1999-08-19 | |
| US149464P | 1999-08-19 |
Publications (1)
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| ES2250177T3 true ES2250177T3 (es) | 2006-04-16 |
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| JP (2) | JP3790472B2 (sl) |
| KR (1) | KR100875222B1 (sl) |
| CN (1) | CN1313465C (sl) |
| AT (1) | ATE307129T1 (sl) |
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| BG (1) | BG65586B1 (sl) |
| BR (1) | BR0013427A (sl) |
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| CY (1) | CY1105253T1 (sl) |
| CZ (1) | CZ2002599A3 (sl) |
| DE (1) | DE60023318T2 (sl) |
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| PT1379525E (pt) * | 2001-02-21 | 2007-12-04 | Astrazeneca Ab | Compostos heteropolicíclicos e sua utilização como antagonistas dos receptores metabotrópicos de glutamato |
| US6916821B2 (en) | 2001-04-02 | 2005-07-12 | Brown University | Methods of treating disorders with Group I mGluR antagonists |
| ES2272754T3 (es) * | 2001-04-02 | 2007-05-01 | Brown University Research Foundation | Uso de antagonistas mglur5 en la fabricacion de un medicamento en el tratamiento de sindrome x fragil, autismo y retardo mental. |
| JP4286146B2 (ja) * | 2001-12-18 | 2009-06-24 | メルク エンド カムパニー インコーポレーテッド | メタボトロピックグルタミン酸受容体−５のヘテロアリール置換ピラゾール系調節剤 |
| JP4299139B2 (ja) * | 2001-12-18 | 2009-07-22 | メルク エンド カムパニー インコーポレーテッド | 代謝型グルタミン酸受容体−５のヘテロアリール置換トリアゾールモジュレータ |
| WO2003053922A2 (en) * | 2001-12-19 | 2003-07-03 | Merck & Co., Inc. | Heteroaryl substituted imidazole modulators of metabotropic glutamate receptor-5 |
| ATE486600T1 (de) * | 2002-03-12 | 2010-11-15 | Merck Sharp & Dohme | Di-aryl-substituierte tetrazol-modulatoren des metabotropen glutamat-rezeptors-5 |
| US7964609B2 (en) | 2002-06-20 | 2011-06-21 | Astrazeneca Ab | Use of mGluR5 antagonists for the treatment of gerd |
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| CN1691944A (zh) * | 2002-08-09 | 2005-11-02 | 阿斯利康(瑞典)有限公司 | 作为代谢型谷氨酸受体－5调节剂的噁二唑 |
| CA2495179A1 (en) | 2002-08-09 | 2004-02-19 | Astrazeneca Ab | Compounds having an activity at metabotropic glutamate receptors |
| AU2003259068B2 (en) | 2002-08-09 | 2009-07-02 | Astrazeneca Ab | "1,2,4"oxadiazoles as modulators of metabotropic glutamate receptor-5 |
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| WO2004089306A2 (en) * | 2003-04-04 | 2004-10-21 | Merck & Co., Inc. | Di-aryl substituted triazole modulators of metabotropic glutamate receptor-5 |
| WO2004103279A2 (en) * | 2003-05-15 | 2004-12-02 | Merck & Co., Inc. | 3-(2-amino-1-azacyclyl)-5-aryl-1,2,4-oxadiazoles as s1p receptor agonists |
| WO2005060961A2 (en) * | 2003-12-18 | 2005-07-07 | Astrazeneca Ab | Treatment of transient lower esophageal sphincter relaxations (tlesrs) and gastro-esophageal reflux disease (gerd) |
| KR101154830B1 (ko) * | 2003-12-24 | 2012-06-18 | 프로시디온 리미티드 | Ｇｐｃｒ 수용체 효능제로서의 헤테로사이클릭 유도체 |
| CA2556320A1 (en) * | 2004-02-18 | 2005-09-01 | Astrazeneca Ab | Fused heterocyclic compounds and their use as metabotropic glutamate receptor antagonists for the treatment of gastrointestinal disorders |
| US7585881B2 (en) * | 2004-02-18 | 2009-09-08 | Astrazeneca Ab | Additional heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists |
| TW200538108A (en) | 2004-02-19 | 2005-12-01 | Astrazeneca Ab | Fused heterocyclic compounds and their use as metabotropic glutamate receptor antagonists |
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